Effects of physiologic soluble agonists on leukotriene C4 production and degranulation by human eosinophils.

The capacities of physiologic soluble agonists to induce leukotriene C4 (LTC4) formation and eosinophil cationic protein release from normal human eosinophils were studied. The most effective stimulus for LTC4 production by eosinophils was N-formyl-methionyl-leucyl-phenylalanine, while that for eosinophil cationic protein release was complement factor 5a. Interleukin-3 (IL-3) and IL-5 modulated both LTC4 formation and eosinophil cationic protein release induced by soluble agonists in a similar fashion, whereas tumor necrosis factor and nerve growth factor affected only LTC4 production. The optimal preincubation period for priming of LTC4 production by IL-3 or IL-5 was 90 min, while that for eosinophil cationic protein release was 10 min. These results indicate that degranulation and the generation of lipid mediators are separately regulated cellular responses, and priming by cytokines may qualitatively change the pathophysiologic consequences of eosinophil activation by soluble agonists.